Gold-Mediated Chemistry Special Issue

Abstract

Published as part of Organic Letters virtual special issue “Gold-Mediated Chemistry”. The unique π-activation ability of gold has long served as the trademark for gold-catalyzed reactions. The reactivity of Au(I) and Au(III) complexes as excellent π-Lewis acids has been well explored by researchers, resulting in a plethora of publications in the past two decades. By leveraging the tunable π-activation properties, researchers continue to explore diverse reactivities such as the functionalization of C–C multiple bonds, enyne cycloisomerization, diyne cycloisomerization, carbene transfer reactions, etc. In recent years, the advances in Au(I)/Au(III) redox catalysis have gained momentum, making gold a potential contender in the realm of transition-metal-catalyzed cross-coupling reactions. In the context of enantioselective gold catalysis, recent years have witnessed the development of ligands for achieving enantioselective Au(I), Au(III), and Au(I)/Au(III) redox catalysis. In addition, merged gold/organocatalysis and gold-based bimetallic systems have emerged as intriguing strategies to achieve enantioselective transformations. The broad reactivity platform exhibited by gold complexes exemplifies their potential for significant applications in the total synthesis of highly functionalized compounds and even complex natural products. This Special Issue collects reports encompassing the diverse aspects of gold chemistry. Xia and colleagues report Suzuki–Miyaura cross-couplings of aryl iodides with aliphatic potassium trifluoroborates to form C(sp³)–C(sp²) bonds. The reaction operates through a Au(I)/Au(III) redox cycle facilitated by a hemilabile (P^N) ligand (DOI: 10.1021/acs.orglett.4c00755). A bifunctional ligand is also used in the gold-catalyzed homo- and heterodimerization of terminal alkynes, as demonstrated by Wu and Zhang. The ligand contains a weakly basic group, specifically a phosphine oxide, which facilitates alkyne deprotonation. This reaction occurs under mild conditions and exhibits excellent selectivity (DOI: 10.1021/acs.orglett.4c01872). Echavarren and co-workers showcase the versatility of Au(I) catalysis in the rapid synthesis of functionalized organic compounds. They present a three-component Au(I)-catalyzed alkoxyvinylation protocol involving acetylene, N-vinyl amides, and alcohols, yielding β-vinyl hemiaminals. Notably, when N,N-bisvinyl amines are reacted with acetylenes, the reaction leads to unique biscyclopropyl pyrrolidines (DOI: 10.1021/acs.orglett.4c02102). Wang and colleagues report the synthesis of a series of C–N and C–C axially chiral N-arylbenzo[g]indoles by exploiting a gold-catalyzed cascade cyclization of chiral diynes, leading to successful central-to-axial chirality transfer. The utility of this method was illustrated by transforming one of the products into a chiral phosphine, which successfully induced chirality in a Pd-catalyzed allylic substitution reaction (DOI: 10.1021/acs.orglett.4c01576). Mansuy, Fensterbank, and co-workers report an enantioconvergent cycloisomerization of racemic 1,5-diynes mediated by a β-cyclodextrin–NHC–Au(I) complex, leading to chiral bicyclo[3.1.0]hex-2-enes with up to 94% ee (DOI: 10.1021/acs.orglett.4c02003). An efficient enantioselective synthesis of 3(2H)-furanones from ynediones has been established by Díez, Fernández, Lassaletta, Monge, and their colleagues. For the cycloisomerization–addition cascade to deliver the products in high yields and enantioselectivities, a key hydrogen-bond activation of a chiral AuCl complex with a sulfonyl squaramide was employed (DOI: 10.1021/acs.orglett.4c02091). Guinchard and co-workers report the use of a chiral bifunctional ligand that enables the synthesis of furan derivatives. The reaction proceeds through a sequential cycloisomerization and nucleophilic attack, via a tethered counterion-directed catalysis (TCDC) strategy. A variety of oxygen nucleophiles such as alcohols, carboxylic acids, and peroxides could be used, enabling the synthesis of diverse chiral furan derivatives with high enantioselectivities (DOI: 10.1021/acs.orglett.4c03521). The synthesis of compounds with heteroatoms that enable further diversification is demonstrated by Requejo, Pérez, Fernández, and colleagues, who report a novel stereoselective gold-catalyzed 4-exo-dig cyclization of N-tosyl homopropargyl amines, leading to borylated (Z)-2-alkylidene-1-tosylazetidines in preparative yields. Under the same conditions, a regiodivergent 5-endo-dig cyclization yielding 2,3-dihydropyrroles could be realized, using N-tosyl homopropargyl amines bearing a propargylic quaternary carbon (DOI: 10.1021/acs.orglett.4c02415). Davies et al. describe a versatile and scalable gold-catalyzed regiodivergent isomerization (1,2 vs 1,3) of propargylic carboxylates containing a thioether moiety and subsequent 1,4 addition of an indole nucleophile. Whereas silver tosylate favors the 1,2 migration, NaBAr^F leads to the 1,3 migration products. Notably, the concomitant addition can be extended to other nucleophiles, such as anilines (DOI: 10.1021/acs.orglett.4c02853). The potential of gold chemistry to be compatible with rather complex systems is nicely illustrated by Hamasur, Hotha, and co-workers in an elegant synthesis of an immunologically active heptamannoside of Mycobacterium tuberculosis with potential application in vaccines. The multistep synthesis involves a sequence of gold-catalyzed glycosylation reactions, among which the recently discovered ethynylcyclohexyl glycosyl carbonate donors are used as key glycosylation partners in key Au/Ag transformations (DOI: 10.1021/acs.orglett.4c00175). With the combination of efforts from researchers around the globe, gold-mediated chemistry holds a great future with exciting discoveries of novel reaction modes and interesting catalytic systems. The discovery of photo- and electro-initiated gold redox chemistry, new ligand design for controlling regio- and stereoselectivity, and promising reactivity associated with multinuclear complexes with active Au–Au bonds are just some examples that have emerged in recent years, which greatly fuel the excitement for the promising future of gold chemistry. The combination of unique gold cation π-activation and these new features will certainly encourage researchers to embark on investigations toward the synthesis of interesting molecular skeletons via alternative methods as well as with improved efficiency and stereoselectivity. Additionally, the functional group tolerance, experimental simplicity, and increasing commercial availability of many catalysts and ligands are important features that will impact the implementation of new gold-catalyzed transformations in industrial settings. It is foreseeable that the newly developed gold complex systems will also strongly impact related fields, from new photocatalyst design to gold-containing drug candidates and molecular probes. With ongoing breakthroughs, gold-mediated chemistry is entering a growth era contributing not only to fundamental organometallic chemistry but also to practical solutions for chemistry, medicinal, and material sciences. Belén Martín-Matute is a Professor in the Department of Chemistry at Stockholm University. Her research centers on catalysis for sustainable organic synthesis, with a focus on developing both homogeneous and heterogeneous catalysts, including functionalized metal–organic frameworks. She focuses on creating highly selective methods that can even be applied to the late-stage functionalization of complex molecules. Since 2021, she has served as an Associate Editor for Organic Letters. She also serves as an advisory board member for ACS Sustainable Chemistry & Engineering, Chemistry─A European Journal, and ChemistryEurope. In 2023, she was elected as a member of the Royal Swedish Academy of Sciences. Nitin T. Patil is a Professor in the Department of Chemistry at IISER Bhopal. He is a synthetic organic chemist with a research focus on homogeneous catalysis. His broad research interests include metal catalysis, organocatalysis, photoredox catalysis, asymmetric catalysis, electrocatalysis, and total synthesis of natural products. Currently, his group is intrigued by the unique reactivities of gold complexes and their applications in advancing synthetic methods, particularly in the formation of nontrivial C–C and C–X bonds. He serves as the Editor of the Elsevier journal Tetrahedron Letters and is a member of the International Advisory Board for the journal Synthesis. María Méndez Pérez is a distinguished scientist and Medicinal Chemistry Group Head in the Integrated Drug Discovery platform at Sanofi, Germany. She has contributed to the delivery of development candidates within different disease areas. Currently, besides providing crucial support to programs within immunology and neurology, she and her team focus intensively on the implementation of novel technologies and workflows. Their primary objective is to expedite the DMTA (Design, Make, Test, and Analyze) cycle, thereby significantly enhancing the efficiency of the drug discovery process. Xiaodong (Michael) Shi is a full Professor in the Department of Chemistry and Biochemistry, University of Maryland College Park. His research focuses on development of new catalytic systems for challenging transformations toward interesting biomedicinal applications and material development. One particular focus of his program is the application of functional 1,2,3-triazoles as ligands in tuning transition metal complex properties for novel catalyst design to achieve challenging transformations with new reactivity. This article has not yet been cited by other publications.